Abstract
AimTo determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania.MethodsSensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB.ResultsSensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline.ConclusionQFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting.
Highlights
The aim of this study was to investigate the potential of the interferon-c release assay (IGRA) QuantiFERONH-TB Gold InTube (QFT) (Cellestis Limited Chadstone, Australia) as a reliable diagnostic tool for physicians in Tanzania, a high TB burden country, with considerable prevalence of HIV and malnutrition, for diagnosing active TB in children
Sensitivity of QFT and TST for Diagnosing Active TB Amongst children, clinically diagnosed with TB and started on anti-TB treatment by the local physician, we found a sensitivity of QFT and TST of only 18% and 12% respectively
In adults HIV infection was negatively associated with a positive QFT result, whilst we found no effect of age, sex or HIV status when analysing risk factors for an indeterminate result
Summary
The aim of this study was to investigate the potential of the interferon-c release assay (IGRA) QuantiFERONH-TB Gold InTube (QFT) (Cellestis Limited Chadstone, Australia) as a reliable diagnostic tool for physicians in Tanzania, a high TB burden country, with considerable prevalence of HIV and malnutrition, for diagnosing active TB in children.TB is a major contributor to childhood morbidity and mortality, with children ,5 years at highest risk and 40–50% of infected infants developing disease within 1–2 years [1,2]. The aim of this study was to investigate the potential of the interferon-c release assay (IGRA) QuantiFERONH-TB Gold InTube (QFT) (Cellestis Limited Chadstone, Australia) as a reliable diagnostic tool for physicians in Tanzania, a high TB burden country, with considerable prevalence of HIV and malnutrition, for diagnosing active TB in children. In TB endemic countries, diagnosis is usually a clinical diagnosis, relying on recognition of clinical features, suggestive chest x-ray (CXR) and if available a positive tuberculin skin test (TST) [4]. QFT relies on M.tuberculosis (MTB) specific T-cell responses, measuring levels of interferon-gamma (IFN-c) released in whole blood in response to stimulation with the MTB specific antigens: ESAT-6, CFP-10 and TB7.7, indicating past or present infection
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